Good Practices for Quality Control Laboratories Part 3 : Working procedures and safety

QC | Slide 1 of 27 2013

Good Practices for Quality

Control Laboratories

Part 3 :Working

procedures and safety

Supplementary Training Modules on Good Manufacturing Practice

QC | Slide 2 of 27 2013

Incoming samples

Sampling procedure and sampling plan

No mix-up or contamination during sampling

Representative of the batch (statistics?)– See also WHO Guidelines on sampling

Records of sampling maintained

Ensure test request accompany sample, and appropriate tests will be used for analysis before testing starts

14.4. , 14.7.

Quality ControlQuality Control

QC | Slide 3 of 27 2013

Test request

Test request form with a sample submitted for testing

Contains information e.g.:

name of the person / sampler

source of the material;

description of the sample / material / product

dosage form, concentration or strength, batch number

sample size 14.5. – 14.6.


QC | Slide 4 of 27 2013

Test request (2)

reason for analysis

date on which the sample was collected

size of the consignment from which it was taken

expiry date / retest date

specification to be used for testing

any other remarks or comments (e.g. discrepancies found or associated hazard) and storage conditions 14.6.


QC | Slide 5 of 27 2013

Registration and labelling

Registration number allocated for every sample

Label affixed to each container of the sample

Information recorded in a register and include e.g.:– registration number of the sample– date of receipt– specific unit to which the sample was forwarded for testing

14.8. - 14.10.


QC | Slide 6 of 27 2013

Visual inspection and storage of the submitted sample

Upon receipt - visually inspect sample. Compare against test request

Record findings, date and sign. Record discrepancies, and queries immediately referred back to the provider of the sample

Samples stored safely

Appropriate storage conditions as required for that sample

14. 11. – 14.12


QC | Slide 7 of 27 2013

Forwarding to testing / work allocation

Sample for testing allocated to analyst or unit

Should have competence, expertise, training

Use specification and test procedure

Verbal requests for testing followed up by written request

14.13 . – 14.18.


QC | Slide 8 of 27 2013

Analytical worksheet

Used by the analyst for recording information about the sample, the test procedure, calculations and the results of testing

Raw data to be attached

Provides documentary evidence either:– to confirm that the sample being examined is in accordance with the

requirements– to support an OOS result and investigation

A separate analytical worksheet for each numbered sample

Different parts (from different analysts/units) kept together15.1. – 15.4.


QC | Slide 9 of 27 2013

Analytical worksheet content:

The number of the sample

Page numbering (e.g. 1 of 10…plus annexes)

Dates (request, start of analysis, and completion)

Name and signature of the analyst

Description of the sample

Reference to the specifications and test methods and limits

Test equipment used15.5.


QC | Slide 10 of 27 2013

Analytical worksheet content:

Reference substance used

Results of the system suitability test

Reagents and solvents employed

Results obtained

Interpretation of the results and the final conclusions

Deviations and other remarks

Approved and signed by the supervisor15.5.


QC | Slide 11 of 27 2013

All values entered immediately on the analytical worksheet

All graphical data attached or be traceable to an electronic record

Completed analytical worksheet signed by the responsible analyst(s), verified and approved and signed by the supervisor

Mistakes and amended results:– old and new information available– signed and dated by the person making the correction– reason for the change given on the worksheet

SOP for amending electronic worksheets and audit trail15.6. – 15.8.


QC | Slide 12 of 27 2013

Selection of the specifications

As in test request or master production instructions (as contained in the marketing authorization or product licence)

Officially recognized pharmacopoeia - current version

Filing / archiving

Kept safely together with any attachments, including calculations and recordings of instrumental analyses

15.9.


QC | Slide 13 of 27 2013

Validation of analytical procedures

All analytical procedures employed for testing should be suitable for the intended use - demonstrated by validation

Validation done according to a validation protocol

Includes analytical performance characteristics e.g. robustness, accuracy and precision

Validation report

Pharmacopoeial methods to be confirmed as suitable for use. If adapted for another use then to be validated 16.1. – 16.3.


QC | Slide 14 of 27 2013

System suitability testing

An integral part of many analytical procedures

Shows that equipment, electronics, analytical operations are appropriate/suitable for the samples to be analysed

To be performed prior to the analysis

In case of a large number of samples analysed in sequence - then appropriate system suitability tests are to be performed throughout the sequence

Verification not required for basic pharmacopoeial methods– E.g. pH, loss on drying and wet chemical methods 16.4.


QC | Slide 15 of 27 2013

In case of a major change (e.g. analytical procedure / composition of the product tested / synthesis of the API) - revalidation may be required

More guidelines and further reading:– WHO TRS 937, Annex 4. 2006 – International Conference on Harmonisation of Technical Requirements for

Registration of Pharmaceuticals for Human Use (ICH)– European Network of Official Medicines Control Laboratories (OMCL)– General chapters of the US Pharmacopeia on Validation of compendial

procedures and on Verification of compendial procedures16.5.


QC | Slide 16 of 27 2013

Testing

Sample tested in accordance with the work plan

If not tested without delay - reasons given in analytical worksheet. Appropriate storage of sample needed

When specific tests are to be done outside the laboratory – test request and samples transferred.

Test procedures detailed and followed

Deviations from the test procedure should be approved and documented

17.1. – 17.3.


QC | Slide 17 of 27 2013

Evaluation of test results

All test results recorded, reviewed and evaluated (statistically where necessary) – check that they are mutually consistent and meeting specifications – signed by analyst and supervisor

Doubtful (atypical) and OOS results investigated (supervisor with the analyst). Checks may include (not limited to):

– Appropriate procedures applied and followed correctly– Discrepancies in raw data; calculations correct– Qualified, calibrated equipment used; system suitability tests were done and acceptable– Glassware, reagents, solvents and reference substances used

Original sample kept until the investigation is complete.

18.1. – 18.2.

18.5. – 18.6.


QC | Slide 18 of 27 2013

Evaluation of test results

Doubtful results can be rejected only if they are clearly due to an identified error

When no obvious cause identified — confirmatory determination is to be performed by another analyst

OOS SOP detailed including allowable number of retests

All investigations and their conclusions recorded

CAPA recorded

18.2. – 18.4.


QC | Slide 19 of 27 2013

Analytical test report is:…

…a compilation of the results and states the conclusions of the examination of a sample

...issued by the laboratory

...based on the analytical worksheet

…free from any amendments18.7 - 18.10


QC | Slide 20 of 27 2013

Content of the analytical test report

Sample registration number and laboratory test report number

Name and address of the laboratory

Name, description, batch number of the sample

Reference to the specifications and procedures used, limits

Results, date of results, and discussion of the results

Conclusion, compliance with specification

Signatures (including head of the laboratory or authorized person)18.11.


QC | Slide 21 of 27 2013

Certificate of analysis (1)

A certificate of analysis is prepared for each batch and contains e.g.:

registration number of the sample; date of receipt;

name and address of the laboratory;

name, description and batch number of the sample

reference to the specification; results of all tests performed (mean and standard deviation, if applicable) with the prescribed limits;

conclusion (within the limits of the specification) 19.1.


QC | Slide 22 of 27 2013

Certificate of analysis contains (2)

Expiry date or retest date if applicable

Date of completion of tests

Signature of the head of laboratory or other authorized person

Note: See also The Guideline on model certificate of analysis19.1.


QC | Slide 23 of 27 2013

Retained samples

As required by the legislation or by the originator of the request for analysis

Appropriate storage conditions

Sufficient amount to allow at least two re-analyses

Kept in its final pack

20.


QC | Slide 24 of 27 2013

Safety (1)

General and specific safety instructions available based on identified risk - in line with national regulations and SOPs

Available to each staff member and supplemented with e.g. written material, poster displays, safety data sheets, audiovisual material, occasional seminars and in line with national regulations and SOPs

No smoking, eating and drinking in the laboratory

Know how to use of fire-fighting equipment

Wear laboratory coats and use eye protection 21.1. – 21.2.


QC | Slide 25 of 27 2013

Safety (2)

Special care - in handling highly potent, infectious or volatile substances

Highly toxic and/or genotoxic samples only in a specially designed facility to avoid the risk of contamination

Containers of chemicals should be fully labelled and include prominent warnings e.g. “poison”, “flammable”, “radioactive”

Adequate insulation and spark-proofing

Cylinders of compressed gases


21.1. – 21.2.

QC | Slide 26 of 27 2013

Safety (3)

Avoid working alone in the laboratory

First-aid materials are provided and staff trained

Protective clothing – e.g. eye protection, masks and gloves, safety showers

Rubber suction bulbs used, safe handling of glassware, corrosive reagents and solvents

Warnings, precautions and instructions

Safe disposal with neutralization or deactivation


21.2. – 21.3.

QC | Slide 27 of 27 2013

Safety (4)

Poisonous and hazardous products

Labeled appropriately

Contact with reagents, solvents, vapours avoided

Limited use of carcinogens and mutagens as reagents

21.4.


Documents

Good Practices for Quality Control Laboratories Part 3 : Working procedures and safety